The field of this invention concerns improvements in the treatment of systemic lupus erythematosus (SLE).
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The present invention provides a method for treating systemic lupus erythematosus (SLE). The method entails administering an effective amount of a pharmaceutically active form of DHEA to an individual with SLE, and at least about 4 weeks after initiating DHEA administration, determining the following disease-activity and constitutional-symptom variables characterizing the individual""s SLE condition: the SLE Disease activity index (SLEDAI), the Systemic Lupus Activity Measurement (SLAM), the Patient Visual Analog Scale (Patient VAS), and the Krupp Fatigue Severity Score (KFSS). The differences between the values for SLEDAI, KFSS, VAS, and SLAM after initiating DHEA administration and baseline values for SLEDAI, KFSS, VAS, and SLAM before initiating DHEA administration are then determined. A decrease in three of these four variables and either a decrease, no change, or an increase of no more that about 5% of a baseline value in the fourth variable indicates that the individual is responding to said DHEA administration. Preferably, the individual is a human SLE patient, and more preferably a human SLE patient with a SLEDAI value greater than 2.
The DHEA polymorphs known as forms I and II are preferred for use in the treatment method of the invention. Accordingly, in preferred embodiments, at least about 85%, and more preferably at least about 95%, of the DHEA administered is present as the form I polymorph, the form II polymorph, or a combination thereof.
In one embodiment, DHEA is administered at a dose and for a period effective to produce a decrease in three of the four disease-activity and constitutional-symptom variables characterizing an individual""s SLE condition and either a decrease, no change, or an increase of no more that about 3% of a pretreatment baseline value in the fourth variable. In another embodiment, DHEA is administered at a dose effective to reduce the risk of an SLE flare at about 200 days of DHEA administration by at least about 5%. Preferably, the method entails administering a daily oral dose of at least about 100 mg, and more preferably about 200 mg, of a pharmaceutically active DHEA. In one embodiment, DHEA administration is continued for a period of at least about 40 weeks.
One advantage of the treatment method of the invention is that is can be combined with other therapies. For example, the treatment method can be carried out with an SLE patient receiving an orally administered drug, such as a glucocorticoid, a non-steroidal anti-inflammatory agent, an immunosuppressant, or an anti-malarial drug. In this case, the treatment method includes continuing administration of the drug during the period of DHEA administration.
The invention also provides a pharmaceutical product for use in treating systemic lupus erythematosus (SLE) in an individual. The pharmaceutical product includes a plurality of doses of a pharmaceutically active form of DHEA, and instructions for performing the treatment method of the invention.
The invention includes the use of the pharmaceutical product of the invention, for treating systemic lupus erythematosus (SLE) in a human patient.
Another aspect of the invention is the use of a pharmaceutically active acid, salt, or ester form dehydroepiandrosterone (DHEA) in the preparation of a tablet-form medicament for use in treating systemic lupus erythematosus (SLE) in a human patient, with a greater than 50% expectation of achieving improvement in the measured values of at least three of the disease-activity and constitutional-symptom variables characterizing a patient""s SLE condition consisting of SLEDAI, KFSS, VAS, and SLAM, and an increase of no greater than 5% of a pretreatment baseline value in the fourth variable, where the change in each variable is determined from the difference between a pretreatment baseline value and values during treatment, when the patient has a pre-treatment SLEDAI value greater than 2, and is treated with a dose of at least about 100 mg per day DHEA, administered orally. In a preferred variation of this embodiment, the patient is treated with a dose of at least about 200 mg DHEA per day for a period of at least about 40 weeks.